Báo cáo y học: "Update on the treatment of ocular toxoplasmosis"

Báo cáo y học: "Update on the treatment of ocular toxoplasmosis"

Int rnational Journal of Medical Scienc s

2009; 6(3):140-142

© Ivyspring International Publisher All rights reserved Short Communication

Update on the treatment of ocular toxoplasmosis

Yan Guex-Crosier

Hôpital Ophtalmique Jules Gonin, Lausanne (Switzerland)

Published: 2009.03.19

Ocular toxoplasmosis is the most frequent cause

of posterior uveitis [1] The parasite has an

intracel-lular cycle During the primary infection, the subject is

usually asymptomatic and can present flu-like

symptoms A dissemination of the parasites occurs

and the tissular cysts will persist during the all life of

the host An ocular reactivation of the disease can

occur when the cysts are present within the retina

(Figure 1) The patients present a photophobia and

floaters are seen The slit-lamp examination reveals

the presence of a granulomatous inflammation, a mild

to moderate anterior chamber inflammation

Fundo-scopy reveals the presence of a yellow focus of

reti-nochoroiditis Recent epidemiological data have

shown that most cases of ocular toxoplasmosis result

from reactivation of ocular toxoplasmosis and not

from primary infection Disease evolution depends on

many factors: the immune response of the host, the

virulence of the parasite and environmental factors

and ocular toxoplasmosis can heals spontaneously

after two to three months even in the absence of

therapy

A review of ophthalmic literature shows that no

standard therapy could be proven by large

multicen-tric clinical trials [2] A survey of the opinion of

oph-thalmic specialists in uveitis was performed recently

by Gary Holland [3] The reasons that were commonly

accepted to introduce a therapy were the following: a)

the presence of a lesion within the vascular arcades of

the posterior pole (zone 1) b) the presence of a lesion

in the proximity of the optic nerve or the macula c) or

a severe inflammatory reaction within the eyes The

zone 1 area was defined as a lesion that was in a

sight-threatning area and corresponding to an area

extending 3000 μm (2 disk diameters) from the fovea

(approximately that area enclosed by the major

tem-poral vascular arcades or 1500 μm from the margins of

the optic disk

The prospective study performed by Perkins in

1956 could not demonstrate the efficacy of daraprim

in the therapy of ocular toxoplasmosis But the out-come was measured 4 weeks after initiation of ther-apy Dihydrofolate reductase inhibitors (DHFR) have shown their efficacy in vivo in the treatment of toxoplamosis To increase the efficacy of therapy a combination of sulfadiazine and pyrimethamine was proposed since synergistic effect of these two drugs could be demonstrated in vitro Pyrimethamine in-terferes with the conversion of folic acid to folinic acid through dihydropteroate synthase (DHPS) whereas sulfonamide interferes with the formation of folic acid from para-amino benzoic acid Human beings unlike

T gondii can utilize exogenous folinic acid for their

cells

Classical therapy of ocular toxoplasmosis con-sists in a association of 2 to 4.0 g of sulfadiazine loading dose given over 24 hours, followed by 1g given 4 times daily associated with 75mg to 100mg pyrimethamine loading dose initially followed by 25

to 50 mg daily Systemic steroids 1mg/kg is associ-ated in the presence of severe ocular inflammation or

in the presence of a zone 1 infection A prospective randomised trial of trimethoprim/sulfamethoxazole versus pyrimethamine and sulfadiazine described a 61% reduction of lesions size was observed in the classic treatment group versus 59% in the TMP/S group Reaction to sulfadiazine therapy is observed in overall 5% of patients The main side effects are crys-talluria, disorders of hematopoietic system hypersen-sitivity reaction nausea and vomiting and depression The sulfadiazine cristalluria occurs in 1-4% of pa-tients The predisposing factors are a poor fluid in-take, fever, diarrhoea, hypoalbuminuria and acidifi-cation of the urine Cofactors in AIDS patients are concomitant use of acyclovir, triamterene or primi-done The leukopenia or thrombocytemia occur in the

presence of interactions with the metabolism of folic

acid Folinic acid therapy is given three times a week

to avoid leukopenia Discontinuation of the therapy is

recommended if the leukocytes are below 4 000 cells

or if thrombocytes are below 100 000 cells

Maculo-papular rush appears in the presence of an

allergy to sulfadiazine

Atovaquone therapy is used as second line

treatment of toxoplasmosis Atovaquone tablets

750mg QID have been given for the treatment of

Toxoplasma retinochoroiditis Azithromycine is an

alternative to classical therapy was proposed as an

alternative therapy in the treatment of ocular

toxoplasmosis The efficacy of the drug was reported

in cerebral toxoplasmosis in AIDS patients The

dos-age used by Rothova et al was 250mg a day or 500mg

every other day and therapy was associated with

pyrimethamine 100mg on the first day that was

fol-lowed by 50mg a day

Prophylaxy of recurrence of toxoplamic

reti-nochoroiditis

Long term intermittent Trimethoprim

/Sulfamethoxazole treatments were used to prevent

recurrences of toxoplasmic retinochoroiditis

Treat-ment was given every three days with a dosage of

60mg trimethoprim and 160mg Sulfamethoxazole

Recurrences were observed in only 6.6% versus 23.6%

in the placebo group However the results were not

tested after 20 months of therapy and long term side

effects are not known

Therapy of toxoplasmosis-associated

ne-ovascular lesions

Toxoplasmosis-associated neovascular lesions

are a rare complication of toxoplasmic

retinochoroid-itis Photodynamic therapy with Visudyne was shown

to block evolution in two out of three patients affected

by neovascularization Ranibizumab was shown to be

a good alternative of therapy in three patients

Geno-type studies and in vitro growth rates and resistance

Genotypic strains of toxoplasma gondii and

re-sistance to medication were recently suspected

De-spite the fact that all clonage lineages can infect

hu-man beings, type II strains are predominant in

Euro-pean and North American population Type III and

recombinant I/III strains are predominant are

pre-dominant in South America Various virulence has

been demonstrated: Type I are highly virulent, type III

strains are intermediate and type I/II are non virulent

Most of pharmacological studies were performed

with RH strains (type I) which was used for its high

capacity to grow in culture A recent paper of Pascale

Meneceur et al has shown that no significant

differ-ence in response to type I, II or III and one atypical strain was observed in the IC50 of the different strains towards pyrimethamine, sulfadiazine or atovaquone therapy A correlation was observed between IC50 of pyrimethamine and strain growth rate

In conclusion, larges randomised clinical studies will be necessary to prove the advantage of one drug toward the other These studies should be completed

by strains analyses and comparison of potential re-sistance toward the antitoxoplasmic drugs

Figure 1: Active retinitis area adjacent to previous

cica-tricial foci

References

1 Holland GN, Lewis KG An update on current practices in the management of ocular toxoplasmosis Am J Ophthalmol 2002;134:102-14

2 Silveira C, Belfort RJr., Muccioli C, et al The effect of long-term intermittent trimethoprim/sulfamethoxazole treatment on re-currences of toxoplasmic retinochoroiditis Am J Ophthalmol 2002;134:41-6

3 Meneceur P, Bouldouyre MA, Aubert D, et al In vitro

suscep-tibility of various genotypic strains of Toxoplasma gondii to

pyrimethamine, sulfadiazine, and atovaquone Antimicrob

Agents Chemother 2008;52:1269-77